Pyran Ring Research Articles

Crystal structure and DFT study of the zwitterionic form of 3-{(E)-1-[(4-ethoxyphenyl)iminiumyl]ethyl}-6-methyl-2-oxo-2H-pyran-4-olate.

The title Schiff base compound, C16H17NO4, crystallizes as a zwitterion, with the phenolic H atom having been transferred to the imino group. The resulting iminium and hy-droxy groups are linked by an intra-molecular N-H⋯O hydrogen bond, enclosing an S(6) ring motif. The conformation about the C=N bond is E and the dihedral angle between the benzene and pyran rings is 70.49 (6)°. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds, forming a three-dimensional supra-molecular structure. There are also C-H⋯π inter-actions and offset π-π inter-actions, involving the pyran rings [inter-centroid distance = 3.4156 (8) Å], which consolidate the three-dimensional structure. Quantum chemical calculations of the mol-ecule are in good agreement with the solid state keto-amine (NH) form of the title compound.

Quorumolides A-C, Three Cembranoids from Euphorbia antiquorum.

Three highly modified cembranoids, quorumolides A-C (1-3), were isolated from Euphorbia antiquorum. Compound 1 is the first example of a cembranoid embedding an α,β-unsaturated-γ-lactone and a tetrahydro-2H-pyran motif within the 14-membered ring. Biosynthetically, it is particularly noteworthy that the stereochemistries of C-2 and C-12 in the pyran ring of 1-3 were opposite to those of marine-derived rare cembranoids.

Pyran-Bridged Indacenodithiophene as a Building Block for Constructing Efficient A-D-A-Type Nonfullerene Acceptors for Polymer Solar Cells.

In recent years, nonfullerene acceptors have attracted much attention, owing to their great potential for use in high-performance polymer solar cells.The ladder-type building block, pyran-bridged indacenodithiophene (PDT), was used for constructing A-D-A nonfullerene acceptors through introduction of oxygen atoms into an indacenodithiophene (IDT) unit. The synthesis of PDT is accomplished by a BBr3 -mediated tandem cyclization-deprotection reaction to construct the pyran ring. Hence, molecular acceptor PTIC was synthesized and used in a polymer solar cell device. Compared to the IDT-based acceptor, PTIC exhibits higher HOMO levels and wider optical band gap at 550-800 nm. Devices fabricated with poly[(2,6-(4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2-b:4,5-b']dithiophene)-co-(1,3-di(5-thiophene-2-yl)-5,7-bis(2-ethylhexyl)-benzo[1,2-c:4,5-c']dithiophene-4,8-dione)] (PBDB-T):PTIC as the active layer give a power conversion efficiency (PCE) of 7.66 %.

A Designed Ladder‐Type Heteroarene Benzodi(Thienopyran) for High‐Performance Fullerene‐Free Organic Solar Cells

To meet the imminent requirement of fullerene‐free electron acceptors, a new ladder‐type heteroarene benzodi(thienopyran) (BDTP) is designed and synthesized by embedding pyran rings in [2,2‐(2,5‐dialkyloxy‐1,4‐phenylene)dithiophene] (PDT) for organic photovoltaic (OPV) applications. Originating from the strong p–π conjugation of the oxygen atom in the pyran rings, electron‐rich BDTP results in the BDTP‐cored molecular acceptor, NBDTP, with strong intramolecular charge transfer effect. With sp3 carbons in pyran rings, NBDTP have the flexibility of targeted modification to resolve the solubility as well as the morphological tuning by handy alkyl chain attachment. As a result, the fusion of pyran rings in BDTP means that the acceptor exhibits a narrow optical band gap of 1.58 eV and a high LUMO energy level of −3.79 eV. Meanwhile, blend morphology of NBDTP‐based OPVs shows fine tunability via thermal annealing. Owing to the beneficial optical absorption, suitable energy‐level alignment, favorable molecule packing, and proper morphology, the optimized NBDTP‐based OPVs achieve a power conversion efficiency of up to 10.1%, which exemplifies the potential of utilizing molecular acceptors featuring ladder‐type heteroarenes for high‐performance OPVs.

Indium-Catalyzed Intramolecular Hydroamidation of Alkynes: An Exo-Dig Cyclization for the Synthesis of Pyranoquinolines through Post-Transformational Reaction.

An efficient approach for the synthesis of pyranoquinolines through the indium-catalyzed activation of alkynes is reported. Intramolecular hydroamidation of alkynes can proceed through alkyne activation by indium(III) and then 6-exo-dig cyclization, leading to a fused pyran ring with high selectivity, high atom economy, and good to excellent yields. The cyclization was accomplished through the oxygen, not the nitrogen, of the amide functional group.

Enhanced Enzymatic Hydrolysis of Lignocellulose by Ethanol- Assisted FeCl3 Pretreatment

The pretreatment and saccharification processes are both the bottlenecks of lignocellulose bioconversion. Pretreatment plays an important role in the saccharification efficiency. In this paper, ethanol-assisted FeCl3 pretreatment was developed to reduce lignocellulose resistance and to enhance the hydrolysis efficiency. The effect of various pretreatment conditions, such as the concentration of FeCl3 and ethanol, pretreatment temperature and time, on the chemical compositions and physical structures of lignocellulose were investigated by scanning electron microscope (SEM), X-ray diffraction (XRD) and Fourier infrared spectrum (FTIR). The increase in the concentration of FeCl3 and ethanol could both boost the degradation of hemicellulose and delignification, respectively. The optimized conditions were obtained, i.e. the concentration of FeCl3 is 0.1 mol/L, the concentration of ethanol is 60 % (v/v), 120 °C and 60 min. The ratio of cellulose conversion at solid loading of 10 % after pretreatment under the optimized conditions reached 96.8 %. And we found that the solution of FeCl3 provided significantly acidic environment, which promoted the degradation of hemicellulose when the pH reached a certain degree (pH 2.5). The iron ions could be absorbed by the pyran ring of carbohydrate to form complex, which may trigger the degradation of carbohydrates and delignification. Our work suggested that the ethanol-assisted FeCl3 pretreatment was very competitive for biomass bioconversion.

Structure of 7-hy-droxy-3-(2-meth-oxy-phen-yl)-2-tri-fluoro-meth-yl-4H-chromen-4-one.

Herein, the synthesis and crystal structure of 7-hy-droxy-3-(2-meth-oxy-phen-yl)-2-tri-fluoro-meth-yl-4H-chromen-4-one, C17H11F3O4, are reported. This isoflavone is used as a starting material in the preparation an array of potent and competitive FPR antagonists. The pyran ring significantly deviates from planarity and the dihedral angle between the benzo-pyran mean plane and that of the exocyclic benzene ring is 88.18 (4)°. In the crystal, O-H⋯O hydrogen bonds connect the mol-ecules into C(8) chains propagating in the [010] direction.

Highly diastereoselective synthesis of novel 2,3,4-trisubstituted chromanes via the reaction of 3-nitro-2-(trihalomethyl)- and 3-nitro-2-phenyl-2H-chromenes with 1-morpholinocyclopentene

The reaction of 3-nitro-2-trifluoro(trichloro)methyl- and 3-nitro-2-phenyl-2H-chromenes with 1-morpholinocyclopentene under the conditions of kinetic or thermodynamic control led to the formation of products due to enamine addition at the C-4 atom of chromene as individual cis,trans- or trans,trans-isomers, differing by the position of double bond in the enamine moiety. Hydrolysis of these compounds in dilute HCl did not cause changes of pyran ring configuration and provided the respective 4-(cyclopentanon-2-yl)chromanes with anti-configuration of hydrogen atoms at the С-4 and С-2′ atoms. Stereochemistry of the obtained compounds was confirmed by X-ray structural analysis.

Abstract 2903: 1-Methoxyphaseollidin: Novel gamma secretase inhibitor targeting notch-1 signaling in breast cancer stem cells

Abstract We recently showed that two different ALDH+ and CD44+/CD24-/low breast cancer stem cells (BSCSs) exhibited stem cell characteristics that include self-renewal, extensive proliferation, the ability to form non-adherent spherical clusters, chemotherapy resistance and high Notch1 expression. We have identified a compound compound: 6-(3-methylbut-2-enyl) coumestrol (Pso) and treatment with Pso resulted in growth inhibition and an EMT phenotype in both BCSCs and BC cells. Oral Pso administration at physiologically achievable doses (25 mg/kg/BW) suppressed the growth of BCSCs and BC xenografts without toxicity. In the current studies, we identified several novel Pso-derived analogs that may be more potent than the parent compound. One such compound, 1-methoxyphaseollidin (1MP), obtained via three main functional group changes: (i) translocation of the isoprenyl moiety from the phenyl ring fused to the pyran ring (as in Pso) to the phenyl ring adjacent to the furan ring, (ii) removal of the carbonyl group from the pyran ring, and (iii) introduction of a methoxy group at the 1-position, inhibited Notch1 activity and growth of both BSCS and BC cells at nM concentration (IC50: 300nM), which is 100 times more potently than Pso in cell culture models. Molecular studies suggest that 1MP inhibits Notch signaling pathways (Hes1, Hey1 and Presenilin) in both BCSC and BC cells. Further, downregulation of AKT signaling (pAKT (S473), p65 and BCl-2 were seen in 1MP treated cells. Docking studies suggest that 1MP binds outside of the catalytic unit of γ-secretase and induces a conformational change, resulting in Notch1 inhibition in both BCSCs and BC cells. More importantly, administration of 1MP significantly inhibited the growth of BCSC and BC tumors without causing gastrointestinal toxicity in tumor-bearing mice. H&E staining suggests that 1MP treated tumors show infiltrate to margins are less as compared to vehicle treated mice’s. We believe targeting notch1 signaling and optimizing 1MP could be an effective therapeutic strategy for treating breast cancer. Note: This abstract was not presented at the meeting. Citation Format: Venkatesh Kolluru, Deeksha Pal, Becca Baby, Houda Alatassi, Arun Kumar Sharma, Murali Ankem, Chendil Damodaran. 1-Methoxyphaseollidin: Novel gamma secretase inhibitor targeting notch-1 signaling in breast cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2903. doi:10.1158/1538-7445.AM2017-2903

Synthesis of some substituted 5H-furo[3,2-g]chromene and benzofuran sulfonate derivatives as potent anti-HIV agents

Synthesized visnagin-9-sulfonyl esters underwent cleavage of their pyran ring upon treatment by hydroxylamine hydrochloride, hydrazine hydrate and primary amines. Reaction of visnagin-9-sulfonyl chloride 1 with alcohols or phenol gave the corresponding sulfonate derivatives 2, that were treated with hydroxylamine hydrochloride, anilines or hydrazine derivatives to give the corresponding compounds 3–5, respectively. The obtained products demonstrated potent anti-HIV activity.

Transformations of 3,3,4-tricyano-3,4-dihydro-2H-pyran-4-carboxamides. Synthesis of pyrano[3,4-c]pyrrole derivatives

A procedure has been developed for the synthesis of polyfunctional pyrano[3,4-c]pyrrole derivatives via intramolecular cyclization involving vicinal cyano and carboxamide groups on a pyran ring. 3-Amino-1-oxo-1,3a,4,7a-tetrahydropyrano[3,4-c]pyrrole-3a,7a-dicarbonitrile thus obtained react with organic amines to give stable ammonium salts and undergo hydrolysis to 1,3-dioxo-1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-3a,7a-dicarbonitriles in the presence of sulfuric acid.

Synthesis of some substituted furo[3,2-g]chromeno[2,3-c]pyrazole and pyrazoline derivatives from 5-hydroxybergapten and 5-hydroxyisopimpinellin as EGFR and VEGFR-2 kinase inhibitors

A series of substituted 7H-furo[3,2-g]chromen-7-one and furo[3,2-g]chromeno[2,3-c]pyrazole derivatives (2–9) were synthesized by using 5-hydroxy-4-methoxy-7H-furo[3,2-g]chromen-7-one (5-hydroxybergapten) and 5-hydroxy-4,9-dimethoxy-7H-furo[3,2-g]chromen-7-one (5-hydroxyisopimpinellin) (1) as starting materials. Compound 1 reacted with amino acid esters to give the corresponding 5-N-amino acid derivatives 2 and 3, respectively. Bromination of 1 gave the corresponding 6-bromo analouges 4, that were treated with amino acids esters to give the corresponding 6-N-amino acids analogues 5. Treatment of the later with hydrazine hydrate led to cleavage of the pyran ring and gave the corresponding pyrazoline benzofuran derivatives 6. Formylation of 1 gave aldehyde derivative 7, which was condensed with amino acid to give the corresponding 5-N-amino-6-formyl derivatives 8. Cyclization of compounds 8 with hydrazine hydrate gave the corresponding pyrazoline derivatives 9. All synthesized compounds were tested as EGFR and VEGFR-2 kinase inhibitors.

A direct FeCl3-catalyzed cross-coupling and cyclization reactions: A new approach to the construction of functionalized pyrano[3,2-a]carbazole derivatives

The FeCl3-catalyzed cross-coupling through a sequential C−N and C−C bond-forming via tandem C−H and N−H bonds functionalization represents a novel method for the formation of dimeric carbazole derivatives. This approach provides a novel dimeric carbazole, namely murrabicine (4), from murrayacine (1). Following the same procedure, a cycloadduct (6) has been achieved due to different substitution pattern at the pyran ring of the mahanimbine (3). This strategy opens up an efficient and direct route to the formation of biologically important pyrano[3,2-a]carbazole alkaloids.

Thiazole-Based σ1 Receptor Ligands: Diversity by Late-Stage C-H Arylation of Thiazoles, Structure-Affinity and Selectivity Relationships, and Molecular Interactions.

Spirocyclic thiophene derivatives represent promising σ1 ligands with high σ1 affinity and selectivity over the σ2 subtype. To increase ligand efficiency, the thiophene ring was replaced bioisosterically by a thiazole ring, and the pyran ring was opened. Late-stage diversification by regioselective C-H arylation of thiazoles 9 a-c resulted in a set of 53 compounds with high diversity. This set of compounds was analyzed with respect to σ1 affinity, σ1 /σ2 selectivity, lipophilicity (logD7.4 ), lipophilicity-corrected ligand efficiency (LELP), and molecular target interactions. The most promising candidates were pyridyl-substituted thiazole derivatives 33 c (2-(1-benzyl-4-ethoxypiperidin-4-yl)-5-(pyridin-3-yl)thiazole) and 34 c (2-(1-benzyl-4-ethoxypiperidin-4-yl)-5-(pyridin-4-yl)thiazole), possessing low-nanomolar σ1 affinity (Ki =1.3 and 1.9 nm), high σ1 /σ2 selectivity (>1500-fold), low lipophilicity (logD7.4 =1.8) and very good ligand efficiency (LELP=5.5), indicating promising pharmacodynamics and pharmacokinetics. Molecular simulation studies, including docking and deconvolution of the free binding energy into its major components, led to decreased hydrophobic stabilization of pyridyl derivatives 33 c and 34 c, which was compensated by lower desolvation energy.

Structural elucidation of condensed tannin from the bark waste of Acacia crassicarpa plantation wood in Indonesia

Recently, Acacia crassicarpa has been planted in peatland areas with acidic soil in Indonesia for use in pulp and paper materials. Its bark is not suitable to produce bleached pulp; hence, it is discarded as waste. Meanwhile, in South Africa and other countries, Acacia mearnsii has been planted for a long time, and its bark extracts have been used as a leather tanning agent. First, the structure of condensed tannin from the bark waste of A. crassicarpa is characterized. The yield of the extracts obtained from A. crassicarpa using a 70% acetone aqueous solution (7% based on bark weight) is less than that obtained from A. mearnsii (34%). A novel flavan dimer from the condensed tannin, specific to A. crassicarpa, is isolated from the bark extracts. To the best of our knowledge, this dimer is a new compound as evidenced from pyrolysis–gas chromatography–mass spectrometry and nuclear magnetic resonance analyses; it corresponds to a gallocatechin–catechin flavan dimer with the absence of one oxygen atom at the 3C of the pyran ring. In addition, 2,4,6-trimethoxybenzoic acid methyl ester is identified as a novel pyrolysis product obtained from the cleavage of the pyran ring.

Methyl (6R*,6aR*,12bR*)-2,4-dimethyl-6-(2-methylphenyl)-1,3-dioxo-2,3,4,6a,7,12b-hexahydro-1H,6H-chromeno[4′,3′:4,5]pyrano[2,3-d]pyrimidine-6a-carboxylate

In the title compound, C24H24N2O6, the mean planes of the pyran rings (AandB) are inclined to one another by 69.2 (1)°, while the aromatic ring (D) of the chromene ring system makes dihedral angles of 63.42 (11) and 66.81 (12)° with the pyrimidine (C) and benzene (E) rings, respectively. Pyran ringAhas an half-chair conformation, while pyran ringBhas an envelope conformation, with the spiro C atom as the flap. In the crystal, molecules are linked by C—H...O hydrogen bonds, forming a supramolecular three-dimensional network. There are also a number of C—H...π interactions present.

A convenient synthesis of carbohydrate derived furo/pyrano[2,3-b]pyrans from 2-hydroxymethyl glycals

An efficient method for the stereoselective synthesis of various linearly fused bicyclic acetals using 2-hydroxymethyl glycals, involving Ferrier type rearrangement and ring-closing metathesis as the key steps, is revealed. The methodology was shown to be very general by applying it to various sugar substrates which lead to the formation of various bicyclic furo/pyrano[2,3-b]pyran ring systems.

Synthesis, spectral and structural characterization of isobutyl 4-(2-chlorophenyl)-5-cyano-6-(((dimethylamino)methylene)amino)-2-methyl-4H-pyran-3-carboxylate

A fascinating selectivity in the direction of the formation of the formamidine was observed upon the reaction of isobutyl 6-amino-4-(2-chlorophenyl)-5-cyano-2-methyl-4H-pyran-3-carboxylate with N,N-dimethyl formamide. A development in selectivity is explored and a probable mechanism for the reaction is also proposed. The formamidine has been analyzed by FT-IR, FT-Raman, LC-MS and NMR (1D and 2D (1H-1H COSY, 1H-13C COSY and HMBC)) spectra. The experimental findings are compared with the theoretical data calculated by using DFT-B3LYP with 6-311++G(d,p) basis set. A good agreement has been observed between experimental and theoretical data. Single crystal X-ray structural analysis of isobutyl 4-(2-chlorophenyl)-5-cyano-6-(((dimethylamino)methylene)amino)-2-methyl-4H-pyran-3-carboxylate (PDMF), evidences the conformation of pyran ring as “flattened−boat”.

Simple and efficient route for the synthesis of functionalized 2,3,7,8-tetrahydro-4H,6H-pyrano[3,2-g]chromene-4,6-diones

A novel series of spiro[chromene-2,1'-cyclohexan]-4(3H)-one derivatives containing either a chalcone or flavanone fragment in their molecules was synthesized. 2'-Hydroxychalcones, containing a spirochromanone moiety, underwent cyclocondensation with formation of a condensed pyran ring. The catalytic efficiency of TFA in the chalcone–flavanone transformation has been demonstrated. The structures of the compounds have been established on the basis of elemental analysis and standard spectroscopic data. The synthesized compounds were tested for their antibacterial and antifungal activities.

New Bicyclic Cembranoids from the South China Sea Soft Coral Sarcophyton trocheliophorum

Nine new bicyclic cembranoids, sarcophytrols M–U(1–9), were isolated from the South China Sea soft coral Sarcophyton trocheliophorum as minor components, along with one known related cembranoid 10. Their structures were elucidated by detailed spectroscopic analysis and chemical conversion. The chemical structures of these metabolites are characterized by the different patterns of the additional cyclization within the 14-member skeleton, which leading to the formation of furan, pyran, oxepane, and peroxyl rings, respectively. Among them, sarcophytrols R and S(6 and 7) share a rare decaryiol skeleton with an unusual C12/C15 cyclization. In addition, the absolute configurations of sarcophytrols M and T(1 and 8) were determined by the modified Mosher’s method. The research of these new secondary metabolites provided a further understanding of the diversity of cyclized cembranoids from the title species.